Pyrazoloacridine Followed by Radiation Therapy in Treating Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme

NCT ID: NCT00006355

Last Updated: 2012-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-05-31
• Study Completion Date: 2006-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of pyrazoloacridine followed by radiation therapy in treating adults who have newly diagnosed supratentorial glioblastoma multiforme.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose, toxicity, and pharmacokinetics of pyrazoloacridine in adults with newly diagnosed, supratentorial glioblastoma multiforme treated with pyrazoloacridine followed by radiotherapy.
• Determine the response rate, duration of disease free survival, and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to type of anticonvulsant (hepatic metabolic enzyme inducers vs hepatic metabolic enzyme moderate inducers or noninducers).

Patients receive pyrazoloacridine (PZA) IV over 3 hours on day 1. Treatment repeats every 3 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Following completion of PZA treatment, patients undergo cranial irradiation 5 days a week for 6 weeks.

Cohorts of 3 patients receive escalating doses of PZA until the maximum tolerated dose (MTD) is determined. Additional patients receive PZA at the MTD.

Patients are followed monthly for survival.

PROJECTED ACCRUAL: A minimum of 3 patients will be accrued for phase I and a total of 18-35 patients will be accrued for phase II of this study.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

pyrazoloacridine

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically proven, newly diagnosed, supratentorial, grade IV astrocytoma (glioblastoma multiforme)

• Incompletely resected disease
• Must have measurable and contrast enhancing tumor on the postoperative MRI/CT scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.7 mg/dL

Other:

• No other serious concurrent infection or medical illness that would preclude study therapy
• No other active malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell skin cancer
• No psychosis requiring ongoing therapy with antipsychotic medication
• Mini mental score at least 15
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy or biologic agents (including immunotoxins, immunoconjugates, antisense compounds, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes, lymphokine activated killer cells, or gene therapy) for glioblastoma multiforme
• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy:

• No prior chemotherapy for glioblastoma multiforme

Endocrine therapy:

• No prior hormonal therapy for glioblastoma multiforme
• Prior glucocorticoids allowed
• Concurrent corticosteroids allowed if on stable dose (no increase within the past 5 days)

Radiotherapy:

• No prior radiotherapy for glioblastoma multiforme

Surgery:

• See Disease Characteristics
• Recovered from immediate postoperative period

Other:

• Greater than 10 days since prior anticonvulsants that induce hepatic metabolic enzymes (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or felbamate)
• No other concurrent investigational agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Glenn J. Lesser, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Josephine Ford Cancer Center at Henry Ford Health System

Detroit, Michigan, United States

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Frenay M, Lebrun C, Fontaine D, et al.: First-line chemotherapy in non resectable low-grade astrocytomas in adults. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-2095, 71b, 2002.

Reference Type: BACKGROUND

Lesser GJ, Carson K, Supko J, et al.: A phase I/II trial and pharmacokinetic study of pyrazoloacridine in adults with newly diagnosed glioblastoma multiforme. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-485, 121a, 2003.

Reference Type: RESULT

Lesser GJ, Carson K, Priet R, et al.: A phase I/II trial of pyrazoloacridine (PZA) in adults with newly diagnosed glioblastoma multiforme (GBM). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-2097, 2002.

Reference Type: RESULT

Other Identifiers

U01CA062475

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NABTT-9804

Identifier Type: -

Identifier Source: secondary_id

JHOC-NABTT-9804

Identifier Type: -

Identifier Source: secondary_id

NABTT-9804 CDR0000068223

Identifier Type: -

Identifier Source: org_study_id